1. Field of the Invention
The present invention relates to a maleimidyl-containing material and a production method thereof. More particularly, the invention relates to a maleimidyl-containing material usable for carriers of diagnosing drugs and pharmaceutical products; carriers for antigen/antibody fixation; chromatographic carriers; viscosity adjustment agents; resin molded materials; coating material additives; crosslinking/curing agents; and additives of cosmetics; and a production method thereof.
2. Description of the Related Art
Functional materials such as ion exchange resins and chelating resins have conventionally been used widely as carriers of various chemical substances. Such functional materials have a variety of reactive groups on the surface. Conventionally, various functional materials, into which active hydrogen-containing groups such as carboxyl, hydroxyl, and primary and secondary amino groups have been introduced, have been employed for various uses. In recent years, biomolecules such as nucleic acids, peptides, and antibodies or synthesized molecules analogous to biomolecules have been employed for affinity chromatography, diagnosing drugs, and inspection drugs while retaining activity and being fixed in materials. For such uses, carriers comprising maleimido groups capable of forming selective and stable bonds with SH groups of the biomolecules or the synthesized molecules analogous to biomolecules in moderate reaction conditions have been sought after. In the case of using materials with such a high selectivity as the carriers, it is required that they evenly and reliably bear a prescribed quantity of maleimido groups and also it is required that the materials have good dispersibility in a water-based medium in which the biomolecules are soluble.
As maleimido-containing compounds, maleimido-containing polystyrene particles are listed up in the 2001/2002 production brochure (p. 909) of Fulka Co. However, these materials have high hydrophobicity and therefore have very inferior dispersibility in a water-based medium.
In such a situation, Japanese Patent Application Laid-Open No. 11-106391 discloses fine particles bearing maleimido-containing phospholipid films on the surface so as not to lower the physiological activity of the biomolecules. The materials are produced as follows: producing in advance a maleimido-containing phospholipid by causing reaction of a bivalent reagent such as N-(6-maleimidocaproyloxy)succinimide having a succinimido group and a maleimido group in one molecule with a phospholipid, and refining the reaction product by column chromatography or the like; producing a maleimido-containing phospholipid film by subjecting the refined product to multi-step treatment; and forming the film on nucleating particles such as magnetic particles. However, the materials have physical disadvantages such as low solvent resistance since the nucleating particles and the maleimido-containing phospholipid films are not chemically bonded. Further, the manufacturing process is extremely complicated and the bivalent reagent, a raw material, is a costly reagent, thus increasing the cost.
As another production method, there is a method for producing the maleimidyl-containing material by reaction of a compound containing two maleimidyl groups in one molecule, such as 4,4′-bismaleimidodiphenylmethane, 1,2-bismaleimidoethane, and 1,6-bismaleimidohexane, with a material containing an SH group.
According to this method, since another maleimido group is further introduced at the time of introduction of one maleimido group, the obtained product becomes a material inferior in dispersibility in a water-based medium. Further, there are disadvantages in that the compound containing two maleimidyl groups in one molecule being a costly reagent results in increased costs and that the material containing the SH group, which is chemically instable, has to be produced in advance.
Further, a maleimidyl-containing material is produced by reaction of polystyrene and N-chloromethylmaleimide by a method described in J. Polym. Sci.: Polymer Chemistry Edition, vol. 17,3675-3685 (1979). According to the method, a maleimido group can be introduced by one-step reaction; however, since the mother material is polystyrene, the hydrophobicity is increased. Also, the method is not desirable in view of the use of harmful phosphorus trichloride to synthesize N-chloromethylmaleimide.
Accordingly, the maleimidyl-containing materials made available so far have been insufficient in the dispersibility in a water-based medium and no production method of a maleimidyl-containing material at a low raw material cost by simple process has been made developed till now.